CLINICAL TRIAL: TREATMENT OF SLEEP PROBLEMS IN CHILDREN WITH AUTISM SPECTRUM DIS

临床试验：自闭症谱系障碍儿童睡眠问题的治疗

• 批准号: 8166701
• 负责人: BOBBI HOPKINS
• 金额: $ 0.88万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166701
• 关键词: Address; Affect; Aftercare; Age; Autistic Disorder; Behavior; Behavioral; Child; Circadian Rhythms; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnostic tests; Disease; Dose; Double-Blind Method; Effectiveness; Evaluation; Exposure to; Family; Functional disorder; Funding; Future; Gastroesophageal reflux disease; Goals; Grant; Hormones; Hour; Individual; Institution; Intervention; Life; Matched Group; Measures; Medical; Melatonin; Oral; Outcome Measure; Parents; Participant; Pharmaceutical Preparations; Phase; Placebos; Play; Production; Quality of life; Questionnaires; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Role; Salivary; Sampling; Severities; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep disturbances; Sleeplessness; Source; Structure; Symptoms; Testing; United States National Institutes of Health; Urine; actigraphy; autism spectrum disorder; experience; hypnotic; improved; primary outcome; randomized trial; response; treatment trial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to examine whether sleep problems in children with autism spectrum disorder (ASD) are related to alterations in the secretion of melatonin (MT), a hormone that plays an important role in regulating the circadian cycle and sleep. Furthermore, we will examine the efficacy of MT for improving sleep in children with ASD. Children with ASD experience high rates of sleep disturbances that potentially contribute to the severity of their cognitive and behavioral dysfunction and to poor quality of life for themselves and their families. It is unclear if irregularities in MT rhythm underlie sleep problems in children with ASD. Their sleep problems are characterized by sleep-wake rhythm abnormalities and symptoms of insomnia including difficulty initiating and maintaining sleep. MT is frequently used to treat these sleep problems; however, its effectiveness as a hypnotic to treat insomnia in children with ASD has not been clearly established. All subjects will be recruited from the Autism Treatment Network after completing rigorous diagnostic testing. Exclusionary criteria include exposure to melatonin in the month prior to the study, current psychoactive medications or medications known to suppress MT secretion, other sleep disorders, such as sleep apnea, and medical disorders that may affect sleep, such as gastroesophageal reflux disease (GERD). Participants¿?? parents will complete a validated sleep questionnaire, which will define the presence or absence of sleep problems. MT onset will be determined by measuring salivary MT levels before and after usual bedtime in ASD children with sleep problems and in a matched group of children with ASD and no sleep problems. Total 24 hour MT production will be determined from urine samples in these same two groups. A double-blind, randomized trial of three oral doses of MT (3, 6, 9 mg) and placebo in children (ages 4-9 years) with ASD and sleep problems will follow a baseline sleep and behavior evaluation. The primary outcome measure will be change in sleep latency as determined by actigraphy at baseline and at the end of the fifth week of each of the treatment trials. Another primary outcome measure will be change in validated behavioral questions given at baseline and during the fifth week of each of the treatment trials. Results from this study will provide a rationale for the development of future trials of circadian rhythm interventions and clinical parameters for the use of MT to manage sleep problems in ASD. Our hypotheses concerning MT are: 1. Children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours; 2. Oral MT will be associated with improvement in sleep and behavior in children with ASD and sleep problems. This is a proposal to study the relationship between melatonin (MT) and sleep problems in children with autism spectrum disorder (ASD), as part of the collaborative research structure of the Autism Treatment Network (ATN). A major goal of the ATN is to conduct clinical research that will have a significant impact on the daily lives and functioning of individuals with ASD and to address immediate concerns of parents. Children with ASD experience high rates of sleep disturbance, which likely contribute to the severity of their daytime cognitive and behavioral dysfunction and to poorer quality of life for them and their families.1, 2 As a step toward addressing sleep problems in ASD, we propose to test two hypotheses. Our first hypothesis proposes that children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours. Our second hypothesis proposes that administration of exogenous MT will result in a decrease in sleep problems and a subsequent improvement in daytime behaviors, with higher doses showing greater effect. This research project has the following specific aims: Specific Aim 1: Characterize the endogenous MT profiles in children with ASD with and without sleep problems. Specific Aim 2: Determine the efficacy of MT used as a hypnotic for improving sleep directly and secondarily improving daytime behavior in children with ASD and sleep problems. We predict that results from this study will reveal lower levels of metabolized MT in children with ASD and sleep problems when compared to ASD children without sleep problems. In addition, we anticipate that children with ASD and sleep problems will have delayed MT onset or altered circadian phase. We predict that participants will experience improved sleep after treatment with oral MT, as indicated by shortened sleep latency. We anticipate that children with altered circadian phase will show better response to treatment with MT. We predict that participants who experience improved sleep will demonstrate improved daytime behaviors as a result of their improved sleep. Data from this study will provide important information concerning circadian rhythm dysregulation in ASD and will support the development of future studies using MT to modify and correct abnormal circadian rhythms.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 我们建议研究自闭症谱系障碍 (ASD) 儿童的睡眠问题是否与褪黑激素 (MT) 分泌的变化有关，褪黑激素 (MT) 是一种在调节昼夜节律和睡眠方面发挥重要作用的激素。此外，我们将研究MT 对改善 ASD 儿童睡眠的功效。 ASD 儿童的睡眠障碍发生率很高，这可能会导致他们严重的认知和行为功能障碍，并导致他们及其家人的生活质量下降。目前尚不清楚这种不规律的情况是否会影响他们的生活。 MT节奏患有自闭症谱系障碍（ASD）儿童的睡眠问题的特点是睡眠-觉醒节律异常和失眠困难的症状，包括启动和维持睡眠，但其作为治疗失眠的催眠药的有效性。尚未明确确定是否患有自闭症儿童。所有受试者都将在完成严格的诊断测试后从自闭症治疗网络中招募，排除标准包括在研究前一个月接触过褪黑激素、当前有效的精神药物或已知的药物。抑制 MT 分泌、其他睡眠障碍（例如睡眠呼吸暂停）和可能影响睡眠的医学疾病（例如胃食管反流病 (GERD)）。 ?? 家长将完成一份经过验证的睡眠调查问卷，通过测量有睡眠问题的 ASD 儿童和匹配的有睡眠问题的儿童在正常就寝时间之前和之后的唾液 MT 水平来确定是否存在 MT 问题。 ASD 和无睡眠问题。将从这两组的尿液样本中确定 MT 的总产量。一项针对儿童（年龄）的三种口服剂量 MT（3、6、9 毫克）和安慰剂的双盲、随机试验。患有自闭症谱系障碍 (ASD) 和睡眠问题的 4-9 岁儿童将进行基线睡眠和行为评估，主要结果指标是通过基线和每次治疗试验第五周结束时的体动记录仪确定的睡眠潜伏期变化。另一个主要结果衡量标准是在基线和每个治疗试验的第五周期间给出的经过验证的行为问题的变化。这项研究的结果将为未来昼夜节律干预试验的开发和使用的临床参数提供依据。 MT 管理睡眠问题自闭症谱系障碍。 我们关于 MT 的假设是： 1. 患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童的 MT 发作会延迟和/或在 24 小时内 MT 分泌减少； 2. 口服 MT 将与患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童的睡眠和行为改善相关；睡眠问题。 这是一项研究褪黑激素 (MT) 与自闭症谱系障碍 (ASD) 儿童睡眠问题之间关系的提案，作为自闭症治疗网络 (ATN) 合作研究结构的一部分，ATN 的一个主要目标是：开展对自闭症谱系障碍患者的日常生活和功能产生重大影响的临床研究，并解决自闭症谱系障碍儿童的睡眠障碍率很高，这可能会导致他们日间认知和行为功能障碍的严重程度。以及较差的生活质量为了他们和他们的家人。1, 2 作为解决自闭症谱系障碍 (ASD) 睡眠问题的一个步骤，我们建议检验两个假设：患有自闭症谱系障碍 (ASD) 和睡眠问题的儿童在 24 小时内会出现 MT 延迟和/或 MT 分泌减少。施用外源性 MT 将导致睡眠问题减少并随后改善日间行为，剂量越高效果越好。 该研究项目有以下具体目标： 具体目标 1：描述有或没有睡眠问题的 ASD 儿童的内源 MT 特征。 具体目标 2：确定 MT 作为催眠药直接改善睡眠并继而改善患有 ASD 和睡眠问题的儿童白天行为的功效。 我们预测，这项研究的结果将显示，与没有睡眠问题的 ASD 儿童相比，患有 ASD 和睡眠问题的儿童的代谢 MT 水平较低。此外，我们预计患有 ASD 和睡眠问题的儿童的 MT 发作或昼夜节律阶段会延迟。我们预测，口服 MT 治疗后，参与者的睡眠会得到改善，睡眠潜伏期缩短表明我们预计，昼夜节律改变的儿童会对 MT 治疗表现出更好的反应。由于睡眠改善而导致的白天行为。 这项研究的数据将提供有关 ASD 昼夜节律失调的重要信息，并将支持未来使用 MT 来修改和纠正异常昼夜节律的研究的发展。